Generation of Human Stem Cell-Derived Pancreatic Organoids (POs) for Regenerative Medicine

  • Victor Navarro-Tableros
  • Yonathan Gomez
  • Maria Felice Brizzi
  • Giovanni CamussiEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1212)


Insulin-dependent diabetes mellitus or type 1 diabetes mellitus (T1DM) is an auto-immune condition characterized by the loss of pancreatic β-cells. The curative approach for highly selected patients is the pancreas or the pancreatic islet transplantation. Nevertheless, these options are limited by a growing shortage of donor organs and by the requirement of immunosuppression.

Xenotransplantation of porcine islets has been extensively investigated. Nevertheless, the strong xenoimmunity and the risk of transmission of porcine endogenous retroviruses, have limited their application in clinic. Generation of β-like cells from stem cells is one of the most promising strategies in regenerative medicine. Embryonic, and more recently, adult stem cells are currently the most promising cell sources exploited to generate functional β-cells in vitro. A number of studies demonstrated that stem cells could generate functional pancreatic organoids (POs), able to restore normoglycemia when implanted in different preclinical diabetic models. Nevertheless, a gradual loss of function and cell dead are commonly detected when POs are transplanted in immunocompetent animals. So far, the main issue to be solved is the post-transplanted islet loss, due to the host immune attack. To avoid this hurdle, nanotechnology has provided a number of polymers currently under investigation for islet micro and macro-encapsulation. These new approaches, besides conferring PO immune protection, are able to supply oxygen and nutrients and to preserve PO morphology and long-term viability.

Herein, we summarize the current knowledge on bioengineered POs and the stem cell differentiation platforms. We also discuss the in vitro strategies used to generate functional POs, and the protocols currently used to confer immune-protection against the host immune attack (micro- and macro-encapsulation). In addition, the most relevant ongoing clinical trials, and the most relevant hurdles met to move towards clinical application are revised.


Cell differentiation Innovative therapies Pancreatic organoids Stem cells Type 1 diabetes mellitus 







Artificial ECM


Alginate-filled hollow fiber bioreactors


High aldehyde dehydrogenase activity


Bioartificial pancreas


β-cell-derived cells


Bone marrow MSC


Calcium peroxide


DNA endonuclease Cas9


Calcium peroxide


Clustered Regularly Interspaced Short Palindromic Repeats




Extracellular matrix




Endothelial progenitor cells


Functional β cell mass


Fetal porcine islet-like cell clusters




Growth hormone releasing hormone


Glucose transporter 2


High aspect ratio vessels


Glycosaminaglycans and heparin enriched capsules


Human embryonic stem cells


Human hepatic progenitor cells


Human induced pluripotent stem cells


Human liver stem cells


Adult human liver stem-like cells


High mobility group box 1


Adult human pancreatic islet mesenchymal stromal cells


Instant blood-mediated inflammatory reaction




Insulin producing cells


Inducible pluripotent cells


Potassium chloride




Methacrylated glycol chitosan


Matrix metalloproteinase




Methoxy polyethylene glycol


Mesenchymal stem cells


Neuronal Differentiation 1 protein


Neonatal islet-like cell clusters


Neovascularized implantable cell homing and encapsulation


Natural Killer T cells


Neonatal pancreatic cell-clusters


Non-obese diabetic


Human pancreatic ductal-cells




PB-TCA alginate-microencapsulation


polyvinyl alcohol/polyvinyl alcohol




Pancreatic and duodenal homeobox 1


Poly(ethylene glycol)


Poly(ethylene glycol) hydrogels containing collagen type I


Vinyl sulfone-terminated polyethylene glycol


Poly(ethylene oxide terephthalate)-poly(butylene terephthalate)


Porcine retrovirus








Polylactic acid




Poly-L-lactic acid-polyvinyl alcohol




Sodium polymethacrylate


Pancreatic organoids


Pancreatic stem cells


Pancreas Associated Transcription Factor 1a






Rotating wall vessels


Silk fibroin macroporous


Semi-interpenetrating polymer network




Sodium percarbonate


Star-shaped polyethylene glycol


Type 1 diabetes mellitus


Type 2 diabetes mellitus


Taurocholic acid (bile acid)




Thread-reinforced alginate fiber for islets encapsulation


Tumor necrosis factor-alpha


Vascular endothelial growth factor


Vascular endothelial growth factor receptor 2


Author Contributions

V.N.T.: contributed to Manuscript writing and Figure preparation; Y.G.: contributed to manuscript writing and Figure preparation; M.F.B.: contributed to Manuscript editing; G.C.: contributed to Manuscript writing and editing.

Conflicts of Interest

The Authors declare no conflict of interest. GC is a component of the Scientific Advisory Board of UNISYTE.


This work has been supported by grants obtained by G.C. and M.F.B. from Unicyte AG.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Victor Navarro-Tableros
    • 1
  • Yonathan Gomez
    • 2
  • Maria Felice Brizzi
    • 2
  • Giovanni Camussi
    • 2
    • 3
    Email author
  1. 1.2i3T Società per la gestione dell’incubatore di imprese e per il trasferimento tecnologico ScarlUniversity of TurinTurinItaly
  2. 2.Department of Medical SciencesUniversity of TurinTurinItaly
  3. 3.Fondazione per la Ricerca Biomedica-ONLUSTurinItaly

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